Advice and Resources for the Biotech Industry

Advice and Resources for the Biotech Industry

Science is a search for truth. I work in the biosciences, where it’s all about understanding the mysteries of life. Our days are built around generating hypotheses and then working to accumulate sufficient data to either prove or disprove them. As scientists, we enjoy problem solving and finding out new things, both expected and unexpected. Our careers are (or should be) built around always doing something novel, because once something hidden is revealed, it’s time to move on to tackling the next riddle. Some of us relish a focus on basic science, while others work in the realm of innovating practical applications for what we (and others) have discovered. One could hardly ask for a more rewarding vocation than that.

Confirmation and applications of our findings are often slow to develop, but that does not negate their value. For example, practical applications arising from the discovery of the double helical structure of DNA by Watson and Crick took decades to turn into something practical. On a personal level, I got a warm feeling of satisfaction when a genetic discovery I reported in my very first science paper in 1980 was finally confirmed at the molecular level 20 years later.

Accuracy and reproducibility are paramount in this process, both in the quality of the data as well as its interpretation. This is what scientists who have good training strive for. Most researchers I know love sitting down with friends and coworkers to go over their data looking for problem areas. Is there something I missed? Is there an alternate interpretation of the data that I haven’t thought of? What additional experiments that I haven’t done would help me distinguish between different possibilities? No one wants to be embarrassed at a conference by an insightful questioner who comes up with an alternate interpretation of the data that you hadn’t thought of. In grad school friends introduced me to the phrase “the simplest interpretation of the data” as a good way to state ones basic viewpoint of what the data means. You’re not ruling out other interpretations of the data (many of which can be quite convoluted). Instead, you’re simply stating what seems the most straightforward way to explain the available information. This is the principle logic that defines Occam’s Razor.

I once gave a 30-minute talk at an international conference, and one of my collaborators came up to me afterwards and told me I had a typo on one of my slides. I was highly embarrassed, even though this had no effect on the data itself or my conclusions. Good scientists focus on getting all of the details right, not just in the data itself, but also in how that information is presented. Any problems reflect poorly on the person giving the presentation. Once I apologized for the error, I profusely thanked him for pointing it out, and I corrected the slide ASAP. He could just have easily said nothing, and I might have continued to show this same slide at future meetings.

Science is a search for the truth, but in practice it isn’t a perfect enterprise. The CRISPR/Cas9 technique for gene editing has been a true scientific breakthrough; it's been widely adopted in labs all around the world. In contrast, a report about an alternative method of gene editing (NgAgo) led to disappointment when others were unable to confirm the original results. The lack of reproducibility of a significant percentage of scientific data remains a confounding problem in the biosciences, for which no simple or affordable solution has yet been found. However, well-trained researchers embrace the idea that this “discover and then confirm or reject” paradigm is what scientific progress is built on. Journal article retractions continue apace (and have actually increased in recent years), some with rather bizarre storylines. The Annals of Internal Medicine recently published a Dear Plagiarist letter written by a scientist whose manuscript was stolen and then resubmitted, by one its reviewers, to a different journal with a new set of authors. This doesn’t imply that the scientific enterprise is rife with fraud, but shows that better training and scrutiny of both scientists and journal reviewers are needed.

The basic concept of truth, however, is under serious assault by politicians and pundits. Truthiness, according to Wikipedia, “is a quality characterizing a "truth" that a person making an argument or assertion claims to know intuitively "from the gut" or because it "feels right" without regard to evidence, logic, intellectual examination, or facts (emphasis added).” The term was coined by comedian Stephen Colbert and was named Word of the Year in 2006 by Merriam Webster. Its use has recently been supplanted by “post-truth”, which was Oxford Dictionaries’ Word of the Year in 2016. It’s defined as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief.”When Science Meets Politics The advantages that a strong foundation of science provides our country were succinctly summed up by Dr. Vannevar Bush, scientific leader of the Manhattan Project, in his prescient 1945 essay Science: The Endless Frontier: “Basic research leads to new knowledge. It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn. New products and new processes do not appear full-grown. They are founded on new principles and new conceptions, which in turn are painstakingly developed by research in the purest realms of science.”More recently Rush Hold, executive publisher of the journal Science and head of the American Association for the Advancement of Science, said, “The scientific process is modern civilization’s best means for arriving at reliable truth. And that process should be allowed to work without political meddling.” President Obama reiterated the importance of undertaking basic as well as applied research in a recent article in Wired, “We must keep funding scientific, technological, and medical research. And above all, we must embrace that quintessentially American compulsion to race for new frontiers and push the boundaries of what’s possible.” Dr. John Holdren, President Obama’s science advisor, recently explained the importance of having a President who is “science-savvy”. The big question ahead of us: will science be respected in the new administration of Donald Trump?

Scientists from a wide variety of disciplines, from astronomy to zoology, all have trepidations about what lies ahead. Climate change scientists in particular are taking defensive measures to protect the data that they have worked so hard to accumulate over the past few decades. What does the future hold? A look at the headlines of some recently published articles lays out the foundations for these fears:

Twenty three hundred U.S. scientists (including 22 Nobel prize winners) sent a letter to president elect Trump urging his administration to not abandon high science standards that are used to inform federal policy decisions. Will he support their agenda? It’s an open question. On the one hand, Trump said during the 2016 Presidential Science debate, “we must have programs such as a viable space program and institutional research that serve as incubators to innovation and the advancement of science and engineering in a number of fields.” He also said, “Science is science and facts are facts. My administration will ensure that there will be total transparency and accountability without political bias.”

Taken at face value this all sounds promising. However, Trump’s nominee to lead the Office of Management and Budget has questioned whether the government should even be funding research at all. If this didn’t happen, of course, one wonders what would happen to industries, such as pharmaceuticals, that are dependent on much of this work coming out of government funded labs for their own development efforts. The possibility that Trump could appoint Jim O'Neill to head the FDA is worrisome. He embraces the idea that companies need not prove efficacy to market their drugs; this would set consumer protections back to a time prior to the passage of the key Kefauver-Harris Drug Amendments in 1962. Another potential Trump nominee, Balaji Srinivasan, suggests replacing the FDA with a "Yelp for drugs." Equally troubling: Trump has reportedly asked Robert F. Kennedy Jr., a believer in the discredited idea that vaccines cause autism, to head up a new commission on vaccine safely and scientific integrity. Trump himself has repeatedly tweeted that vaccines cause autism. And Trump’s record of making outrageous statements without a shred of evidence to back them up (such as his assertion that he actually won the popular vote if you subtract out the millions of illegally cast ones) is extremely worrisome. He’s clearly living in the post-truth world.

Political Decisions at the FDA

Cracks in the political façade of the FDA were recently illustrated by the approval of Exondys 51, Sarepta Therapeutics’ Duchenne muscular dystrophy drug. Many think the agency surrendered to pressure brought on by a strong community of patient families. This decision by Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research, was widely panned by both the medical community as well as numerous individuals within the agency itself. The basic point of contention here was the failure of the clinical study (involving a very small number of boys treated over a relatively short period of time) to show an actual clinical benefit. The less-than-compelling data has emboldened several insurance companies (who nearly always pay for these rare disease drugs) to either deny coverage for the drug or to severely limit its use. Some people have described the medicine as little more than a $300,000 placebo, and critics worry that the availability of this drug will make it that much harder to develop more effective medicines in the future.

Be A Science AdvocateAll of us must remain vigilant to the machinations of science denial campaigns. Sean Carroll, UW-Madison professor of Genetics and Molecular Biology, put together a “manual” of Science Denialism, the essence of which is, “First, cast doubt on the science. Second, question the personal motives and integrity of the scientists. Third, magnify genuine disagreements among scientists, and cite non-experts with minority opinions as authorities. Fourth, exaggerate the potential harm caused by the issue. Fifth, frame the issue as a threat to personal freedom. And sixth, claim that acceptance would repudiate a key philosophy, religious belief, or practice of a group.” Surgeon and writer Atul Gawande recently delivered a thoughtful commencement address for Cal Tech in which he explains the process of thinking like a scientist, how a mistrust of science has developed, and how we can work to regain this trust.Science is unquestionably important in our modern world. Fake news, along with poor quality science journalism, make it much more difficult to demonstrate this fact to the public. It’s not just that science helps us to understand the universe around us. It’s the primary way that we figure out what changes we might be able to undertake to make our world a better place. This can involve combatting climate change so those who live in low-lying areas don’t drown as the ocean levels rise. It’s developing both preventive and treatment strategies to combat infectious diseases, including AIDS, Zika, and Ebola. Vaccines, for all of the misleading stories circulating on the Internet about them, are clearly one of the greatest life saving inventions ever developed by mankind. Science and technology enable us to provide clean water as well as grow food for those who currently don't have a sufficient supply. Science isn’t interested in your color, creed, race, religion, gender, or economic status, and can help all of us across a wide variety of disciplines. In the end, if we allow science to be marginalized by our leaders we will have a terrible price to pay. Critical thinking cannot be replaced by “open mindedness.” The net result could mirror what cartoonist Bill Watterson illustrated: when an immature and unqualified individual controls the levers of power, Scientific Progress Goes “Boink”, and even Calvin and Hobbes’s fantastical Transmogrifier will not be able to save us. Wouldn’t it be nice if the President-elect and his appointees could use the Cerebral Enhance-O-Tron to gain a greater understanding and appreciation of science? Sadly, this device also doesn’t exist, and therefore can’t be an effective solution to willful ignorance. Serious problems deserve thoughtful efforts to solve them, and we must all continue to lobby for science to be respected by this new administration.

Follow me on Twitter @lymanbiopharma to ensure you don't miss any of my blog posts!